The overall objective of the proposed research is to determine whether the endogenous analgesic system originating in the midbrain periaqueductal gray (PAG) is significantly influenced by structures of the limbic forebrain--in partiicular, the hippocampus and amygdala. The PAG has been shown to specifically inhibit the central transmission of peripheral noxious stimuli via relays in nucleus raphe mgnus and the dorsolateral funiculus of the spinal cord. PAG neuronal activity is presently being studied in association with electrical stimulation of the hippocampus and amygdala in the awake of primate with the use of extracellular microelectrode techniques. If a major influence on PAG neurons is found in the present study, then for the first time, evidence for a major central forebrain mechanism capable of modulating this endogenous analgesic system will have been provided. In addition, a potential model in the awake primate will have been developed for evaluating the pharmacological role of agents known clinically to be beneficial in pain syndromes via their influence in the limbic system as wellas the role of opiates and opiate blocking agents.